Biomedical subjects
Publications and source records attributed to D Lambert.
Magnetic resonance imaging has proven to be a useful tool for imaging the paranasal sinuses and nasal cavities. Of particular interest in this region is the ability to distinguish between lesions that are highly cellular with little free water (neoplasms) and lesions that have significant amounts of serous and mucinous secretions and thus contain predominantly free water (infections).
Allergic contact dermatitis to gold and its alloys is a rare affection and it is difficult to interpret gold salts patch tests. We report two cases of patients with positive patch tests to 0.5% sodium aurothiosulfate discovered during a dermatology exploration of an occupational contact eczema (for the first patient) and an intolerance to gold jewelry (for the second). There is much confusion in the literature concerning the allergologic exploration of contact dermatitis to gold: no standardized test, possible cross reactions between different gold salts, the tests often irritate. The mechanism of sensitization to gold salts is unknown since pure gold is inalterable and does not contain any salts. The pertinence of a positive test to one or more gold salts must therefore be examined carefully and the diagnosis of gold allergy must not be made without sufficient evidence.
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In rat liver homogenates fortified with the appropriate cofactors (ATP and CoA), valproic acid induced H2O2 production rates by far lower than those recorded on the straight medium-chain fatty acid n-octanoic acid. Using directly the CoA esters of these carboxylic acids as substrates for the rat liver H2O2-generating enzyme activities, valproyl-CoA, and n-octanoyl-CoA were found to induce similar oxidation rates. In the rat liver homogenates, cyanide-insensitive valproyl-CoA and octanoyl-CoA oxidations occurred at rates similar to those of valproyl-CoA and octanoyl-CoA oxidase(s), respectively. Studies on fractions obtained from rat liver postnuclear supernatants by isopycnic centrifugation on a linear sucrose density gradient disclose that the density distribution of valproyl-CoA oxidase superimposes to those of catalase, fatty acyl-CoA oxidase and cyanide-insensitive fatty acyl-CoA oxidation, three peroxisomal marker activities. By contrast, the cyanide-insensitive valproyl-CoA oxidation does not adopt the typical peroxisomal distribution of these activities but rather exhibits a mitochondrial localization with, however, a minor peroxisomal component. Interestingly enough, the comparative study of rat tissue distribution, inducibility by clofibrate and sensitivity to deoxycholate indicated that valproyl-CoA oxidase is an enzyme distinct from fatty acyl-CoA oxidase and bile acyl-CoA oxidase. Taken as a whole, the results presented here support the occurrence of a peroxisomal oxidation of the CoA ester of valproic acid and its delta 4-enoic derivate which might be characterized by two major features: initiation by an acyl-CoA oxidase distinct from fatty and bile acyl-CoA oxidases, and inability to complete the beta-oxidation cycle which would not proceed, at significant rates, further than the beta-hydroxyacyl-CoA dehydrogenation step in peroxisomes.
The distribution of venous reflux in patients with skin changes associated with chronic venous insufficiency presenting to a specialist clinic was assessed. A total of 300 limbs in 153 patients were examined by Doppler ultrasonography with colour-flow imaging for the presence of venous reflux in superficial veins, deep veins and medial perforating veins, both above and below the knee. Ninety-eight limbs had skin changes, which included hyperpigmentation, lipodermatosclerosis, atrophie blanche and ulceration. Of this group, 2 per cent had no evidence of venous reflux on duplex scanning, 39 per cent had deep vein incompetence, 57 per cent had superficial vein incompetence and 2 per cent had isolated medial perforating vein reflux. Of 25 limbs with ulceration, 13 had superficial and 12 deep vein reflux. A total of 202 legs, which included 20 normal control limbs, had no skin changes; 22.3 per cent of these had no venous reflux, 8.4 per cent had deep vein incompetence, 65.3 per cent had superficial incompetence and 4.0 per cent had isolated medial calf perforating vein incompetence.
The present work was aimed at defining novel strategies to reverse chemoresistance to anticancer drugs, especially by interfering with cellular glutathione metabolism, peroxisomal and/or extraperoxisomal hydroperoxide metabolic pathways. Preliminary results are presented about molecules we demonstrated to be capable of interfering with hydrogen peroxide metabolism in cells. Prior to describing these molecules, a short overview of glutathione and free radical metabolic pathways is presented as well as a rapid presentation of the characteristics of chemo-sensitivity and -resistance towards the anticancer drug adriamycin, with special emphasis on hydrogen peroxide metabolism. The strategies currently developed to reverse chemoresistance are further presented in subsequent sections, our own strategy to achieve inhibition of hydrogen peroxide breakdown and stimulation of peroxisomal hydrogen peroxide production is illustrated on the basis of molecular modelling studies and biochemical investigations on extraperoxisomal and peroxisomal metabolic pathways. Preliminary studies on cultured cells have been initiated. The perspective for future studies is presented as well as other possible models of chemoresistance as target for the design of hydrogen peroxide metabolism-interfering pharmacomolecules.
The concentration of plasma vitamin B12 bound to transcobalamin II was measured by two methods: QUSO and Heparin Sepharose (HS). The new HS procedure provided a specific, direct measurement of vitamin B12 bound to both R binder and transcobalamin II in plasma.
Bufexamac is an anti-inflammatory agent used as topical treatment of various pruritic diseases. Since it was put on the market, this product has been blamed for the occurrence of contact dermatitis (eczema, urticaria) and, rarely, severe toxicodermia. We report a case of severe contact dermatitis developed after application of bufexamac (Parfenac) cream. Patch-tests performed two months after the acute phase were positive (+ + +) for both Parfenac cream and bufexamac.
Ionophoresis is a well-established treatment for idiopathic hyperhidrosis. Modern apparatuses are reliable as long as the electrical equipment is used correctly. The authors present five cases of cutaneous incidents resulting in burns and secondary necrosis. Two of the cases could be explained by defective protection and the other three were apparently of the same type although non confirmation could be established. In comparison with uneventful incidences (pruritus, erythematous reactions, dysaesthesia) these spectacular burns should not exist. Machines must be regularly check and only electrodes with optimal protection should be used.
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We report the case of a 60-year old man who, during four years following surgical repair of an inguinal hernia (with transient antithrombotic therapy), suffered from an atypical inflammatory nodule on the dorsum of the left foot with an erythematous plaque on the first intermetatarsal space, together with an inflammatory plaque on the right fifth finger and hairless plaques on both wrists. An ultimate biopsy of the nodule made it possible to discover, unexpectedly, two shadows of cholesterol crystals in a vascular lumen and inside the cytoplasm of a giant multinucleate cell found on a single histological slice and at the deepest part of the fragment. The inflammatory lesions disappeared under a 250 mg/day aspirin treatment. We emphasize the uncommon clinical and pathological pseudo-lymphomatous features of this case and regard our description as original in view of the chronicity of the embolising process.
Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in the control of cell growth and proliferation. By employing androgen action in the prostate as a model of growth control, we have previously documented that androgens modulate prostatic CK-2 activity in a tissue specific manner. Here we have investigated the role of transcriptional control of prostatic CK-2 in androgenic regulation of its activity. We first cloned and sequenced full length cDNAs encoding the alpha and beta subunits of rat CK-2. The cDNA sequence encoding the alpha subunit corresponded with previously reported sequences for other species, as well as with the derived partial amino acid sequence reported for a rat cDNA. The cloned cDNA for rat CK-2-beta subunit, not reported previously, was also identical in amino acid sequence to that of other species. The cDNAs for alpha and beta subunits were employed as probes to examine the effects of altered androgenic status on transcription of mRNAs for the subunits of prostatic CK-2. Androgen deprivation caused a slow decline in transcription of the a subunit, so that no change was noted at 24 h postcastration; however, at later periods of androgen deprivation a progressive but relatively slow decline was apparent. Administration of a single dose of 5 alpha-dihydrotestosterone (5 alpha-DHT) to 6-d castrated animals did not elicit an early expression of new mRNAs for CK-2-alpha and beta subunits. However, a significant expression of mRNAs for the two subunits was apparent at 8 h (i.e., later stages of the prereplicative phase) reaching a peak in the proliferative phase of prostatic growth (i.e., at 24-48 h) following androgen administration. These data suggest that androgenic regulation of CK-2 gene transcription is not an early event related to androgen action, but is substantial in the prereplicative phase of prostatic cell proliferation mediated by androgen. Further, androgenic stimulation of the mRNA expression for the alpha and beta subunits of CK-2 appears to be differential.
The authors present 3 cases of melanoma associated with a parathyroid adenoma discovered by routine measurement of blood calcium levels. The melanomas were differently located and had different histological degrees. Hypercalcaemia is an infrequent complication of melanoma. According to data found in the literature, it is most often consecutive to bone metastases. The other causes of hypercalcaemia are metastatic extension of melanoma to the parathyroid glands, secretion of parathormone-related peptide (PTH-RP) and the actions of prostaglandins, vitamin D and the osteoclast-activating factor (OAF). Primary hyperparathyroidism due to adenoma has seldom been described associated with melanoma.
This report details the case of an atopic patient showing a photosensitivity caused by a hexamidine solution. Patch tests were negative but photopatch tests to hexamidine in water solution were positive, after irradiation by ultraviolet A (UVA); all control tests were negative. It is well-known that hexamidine can induce contact allergy but this case was the first reported in which UVA was implicated. This photoallergy can be explained by the structure of the hexamidine molecule, but the question is: why has there never been such a case reported before?
Our randomised study in parallel groups, double-blind double placebo, has compared the efficacy, onset of action and safety of terfenadine and cetirizine in chronic idiopathic urticaria. Over a fourteen day period, patients of the first group received a tablet containing 120 mg of terfenadine, those of the second group a tablet containing 10 mg of cetirizine. Symptoms were assessed every two hour period for the ten first hours on the first day (D1), and before and at the end of the study by the investigators. 193 patients were included by 48 dermatologists between May 1989 and July 1990. Both groups were well matched for all general characteristics and baseline symptoms scores. The onset and the intensity of regression of symptoms (pruritus, erythema and discomfort during sleeping time) were similar in both treatment groups public physicians: improvement of pruritus in over 90% of the patients. Meanwhile the tolerability was good or excellent for dermatologists and allergologists for 92% of the patients under terfenadine against 81% of the patients under cetirizine (p < 0.05). Adverse events (fatigue and drowsiness) were significantly reported less frequently (p < 0.05) in patients on terfenadine (19%) than on cetirizine (33%). This study confirms the efficacy of terfenadine compared with cetirizine in the treatment of chronic idiopathic urticaria. Adverse events were less significant for terfenadine (n = 18) than for cetirizine (n = 29) (p < 0.05).
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A theoretical model was developed taking into account the production and destruction of oxygen-derived free radicals. The steady state of the system was derived by using the rate equations of these reactions, and the stability of the system was tested. In the simplified model, only one stable steady state was found. However, we know that glutathione peroxidase can be inhibited by hydroperoxides, and, when incorporated into the model, this effect led to a complex situation with the presence of some stable and some unstable domains according to the concentration of either the enzyme or the hydroperoxide. This qualitative description of the system was compared with experimental data on the protection given by three antioxidant enzymes, and concordance of data was found which allows some quantification of the system. A general view of the efficiency of the three antioxidant enzymes and of the stability of the system according to their concentrations could be produced.
Before establishing a community leg ulcer programme, a survey was performed to assess the incidence and prevalence of lower limb ulceration in the Newcastle Health District. The prevalence was 1.9 per 1000 in patients over the age of 45 years, and the annual incidence 3.5 per 1000 in the same age group. Recurrent ulcers represented 47 per cent of the total and 50 per cent of all ulcers had been present for > 6 months. District nurses spent 190 h per week in the community dressing leg ulcers, making a total number of 25,922 visits each year. In the treatment of leg ulcers 35 different types of dressing were used and only 14 per cent of ulcerated limbs were treated by appropriate compression. Of all patients with leg ulcers, 35 per cent had been seen by a hospital specialist but only 7 per cent had been examined by a vascular surgeon at any time.